Increasingly, women are asthmatic in pregnancy and their children are at higher risk. Yet little is known about perinatal risk factors that effect asthma development in young children. Environmental exposures (e.g., aeroallergens, tobacco smoke, air contaminants) are known risk factors for asthma severity in children and atopic asthma is understood to relate to immune status, particularly total IgE response, but in complex and little understood ways. Several candidate genes are suggested which may increase risk of atopy and/or asthma. This application explores in-utero, perinatal and neonatal risk factors, poor maternal asthma management, genotype, immune status, lactation, and their interactions on infant asthma development, in a population of children whose experience in-utero was extensively monitored in 873 asthmatic and 1336 control mothers. At age 5, we will ascertain asthma diagnosis and severity in these children. In-utero and perinatal risk factors have been obtained prospectively and include obstetrical and delivery history, history of maternal asthma (measured by spirometry, symptoms, medication) and infections, prenatal medication history, maternal smoking history, job exposures and home characteristics (humidity, molds, pets, heating sources). The child's immune status at birth will be assessed by stored cord blood total serum IgE. From cheek swabs, neonatal polymorphisms B2 adrenergic receptor (Arg 16-Gly or Gln27-Glu), promoter region of the IL-4 gene, particularly at TT, Rsa-1 polymorphisms in the beta chain of the high affinity receptor for IgE (Fc epsilon RI-beta), tumor necrosis factor complex (LTalpha-Nco I, and TNF-308), CD14, IL-13, and IL-4 receptor will be assessed. Lactation, changes to housing characteristics, neo- and post-natal risk factors will be measured retrospectively by medical records and interview. Detailed characterization of maternal asthma and perinatal risk factors, and inclusion of black (10 percent) and Hispanic (19 percent) mothers, make this a unique "pregnancy cohort" for better understanding asthma onset in young children. Identification of pregnancy and neonatal risk factors for infant asthma may offer opportunities for early prevention.